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Biomedical subjects

L Adler

Publications and source records attributed to L Adler.

At least 37 records · Page 2Linked to original sources

Chemical precipitation of apolipoprotein B-containing lipoproteins facilitates determination of LDL particle size.

OBJECTIVES: To simplify the determination of low-density lipoprotein (LDL) particle size by eliminating the need for ultracentrifugation. DESIGN AND METHODS: We compared LDL particle size determination by gradient gel electrophoresis using two different methods for separation of LDL: (a) by ultracentrifugation with a density between 1.019 and 1.063 g/mL, and (b) by precipitation of the apolipoprotein B-containing lipoproteins from plasma. LDL particle size was determined for 41 individuals using both methods. RESULTS: The correlation between these two methods was r = 0.98; peak particle diameter (nm) was reproducible with a coefficient of variation of 1. 3% for LDL separated by ultracentrifugation and 1.4% for LDL prepared by precipitation. The intra-assay variation within a single gel was 0.2%. CONCLUSION: Elimination of the need for ultracentrifugation or lipid staining significantly reduces the cost and simplifies the procedure of LDL particle sizing. As a result, larger patient populations can be more readily screened for the determination of LDL particle size.

Adult↗

Leaky wave detection at air-solid interfaces by laser interferometry

A recently developed optical heterodyne interferometer is proved to be sensitive to detect ultrasonic waves leaking out from metals (and from non-metals as well) several centimeters away from the metal surface in air. This measurement is based on the detection of the optical index variation in air due to the leaky wave. Experiments were carried out using both ultrasonic leaky Rayleigh and leaky Lamb waves in the low-megahertz region. Optical measurements of these leaky wave velocities in semi-infinite materials and plates, which are related to elastic constants of the materials, showed a good correlation to the predicted values. Optical measurements of the amplitude of the leaky waves were used to obtain attenuation coefficients, which correlate to the structural integrity of the materials. Surface and near-surface defects were also detected. This optical method can be used for metals with low-reflectivity surfaces. Thus, it can be used for non-polished surfaces and can be extended for non-contact, non-destructive evaluation applications.

Journal Article↗

October 18, 2000 8:30-8:45. Problem Solving with FDG Positron Emission Mammography.

Purpose: To examine one potential clinical application of dedicated devices for positron emission mammography.Background: Dedicated devices for breast imaging with FDG have technical specifications that appear well-suited for detecting small breast cancers, including registration with x-rays, high count sensitivity, and spatial resolution in the 2-3 mm range.Methods: In IRB-approved clinical trials, patients who were scheduled for biopsy for suspicious findings on x-ray mammograms were injected with 10-20 mCi FDG intravenously one to two hours prior to x-ray guided core biopsy or lumpectomy. Positron emission mammograms using a dedicated device were performed just before biopsy, and results compared to final histopathology.Results: Three patients whose cancers were missed on initial x-ray mammograms or whose mammograms contained subtle abnormalities that were not strongly suspicious for cancer, were shown to have very suspicious hot spots on positron emission mammograms. These patients were later confirmed to have cancer.Discussion: The role for dedicated devices for positron emission mammography is evolving. Finding cancers that are either mammographically occult or have low indices of suspicion is a potential application for this technique. Further clinical and technical work will be needed to better define the strengths and weaknesses of the device in this application.

Journal Article↗

Effect of labeling of plasma lipoproteins with [(3)H]cholesterol on values of esterification rate of cholesterol in apolipoprotein B-depleted plasma.

The fractional esterification rate of cholesterol in apolipoprotein B (apoB)-depleted plasma (FER(HDL)) is a good indicator of particle size distribution in high density lipoprotein (HDL) and low density lipoprotein (LDL). However, there has been a discrepancy in the absolute values of FER(HDL) published by different laboratories. Because the main difference between the methods was in the labeling of lipoproteins with [(3)H]cholesterol we investigated the effect of using Corning immunoplates and paper discs as carriers of the labeled unesterified cholesterol. We found that Corning plates trap some (3)H-labeled free cholesterol, which is released during incubation at 37 degrees C. This means that this additional (3)H-labeled free cholesterol is exposed to lecithin: cholesterol acyltransferase (LCAT) for a shorter time and artificially decreases FER(HDL). Using paper discs discarded before incubation as carriers of the (3)H-labeled free cholesterol results in complete labeling of HDL and thus yields higher values of FER(HDL).

Apolipoproteins B↗

The effect of iron limitation on glycerol production and expression of the isogenes for NAD(+)-dependent glycerol 3-phosphate dehydrogenase in Saccharomyces cerevisiae.

When deprived of iron, Saccharomyces cerevisiae rearranges its metabolic flux towards increased glycerol production. This work examines the role and regulation of GPD1 and GPD2, encoding two isoforms of glycerol 3-phosphate dehydrogenase, in glycerol production during iron starvation. The two genes respond differently on transfer of cells to iron-limited conditions. Whereas the expression of GPD2 increases about 3-fold, that of GPD1 does not exhibit significant changes. Deletion of either GPD1 or GPD2 alters the capacity for glycerol production during iron-limited as well as iron sufficient conditions. However, loss of function of either gene does not seem to provoke compensatory flux via the other gene product. As judged from the glycerol production, the amount produced by each single mutant adds approximately up to the level produced by the parental strain. In agreement with the pattern of expression of GPD2, this gene product was estimated to account for the bulk of the glycerol production (about 60%) during iron-limited conditions. The strong growth inhibition caused by iron starvation was reversed by the addition of iron also for a gpd1Deltagpd2Delta double deletion mutant, which is unable to produce any detectable glycerol.

Gene Deletion↗

Health care providers and purchasers and evaluation of interactive health communication applications. Science Panel on Interactive Communication and Health.

Health care providers and purchasers of health services have an opportunity to improve patient care and potentially save costs through the wise purchase of interactive health communication applications for patients and employees. Purchasing decisions based on evaluation and evidence should drive the design and development of new systems. The cycle of evaluation includes a needs assessment before system development, usability testing during development, and studies of use and outcomes in natural settings. This type of evidence is critical to our understanding of how best to provide health information and decision assistance to patients, employees, and others.

Community Participation↗

Attention and memory dysfunction after traumatic brain injury: cholinergic mechanisms, sensory gating, and a hypothesis for further investigation.

Traumatic brain injury (TBI) is a common occurrence, with a rate of nearly 400,000 new injuries per year. Cognitive and emotional disturbances may become persistent and disabling for many injured persons, and frequently involve symptomatic impairment in attention and memory. Impairments in attention and memory have been well characterized in TBI, and are likely related to disruption of cholinergic functioning in the hippocampus. Additionally, disturbances in this neurotransmitter system may also account for disturbances in sensory gating and discriminative attention in this population. The electroencephalographic P50 waveform of the evoked response to paired auditory stimuli may provide a physiologic market of impaired sensory gating among TBI survivors. The first application of this recording assessment to the TBI population is reported. Preliminary findings in three cases are presented, and the interpretation of impaired sensory gating in this population is discussed. Given the impact of TBI on cholinergic systems, the effects of cholinergic augmentation on attention and memory impairment, and the availability of an electrophysiologic marker of cholinergic dysfunction responsive to cholinergic agents, a testable cholinergic hypothesis for investigation and treatment of these patients is proposed.

Acetylcholine↗

[Not Available].

With the increasing application of imaging techniques, characteristic changes in the structure and functional activity of certain neuronal networks and transmitter Systems have been discovered in the brains of patients suffering from various psychiatric disorders. These findings have often been assumed to support biological concepts of the genetic background and causation of these disorders. However, several lines of research are converging to indicate that the initially established genetically programmed neuronal Connectivity is further elaborated, fine tuned and modified by usedependent neuronal and synaptic plasticity. In all socially organized species in general and in human subjects in particular, psychosocial experiences appear to represent the most important trigger of use-dependent adjustments of neuronal Connectivity through the facilitation, modification and reorganization of neuronal networks. In experimental animals, changes in psychosocial rearing conditions were shown to cause profound and persistent changes in the cytoarchitecture, dendritic arborization and synapse formation in individual brain regions as well as in the maturation of monoaminergic afferences. Based on these findings, the mechanisms of the biological affixation of psychosocial experiences are described and the implications of experience dependent neuronal and synaptic plasticity in the prevention and the therapy of mental disorders are outlined.

Attachment↗

The Saccharomyces cerevisiae SOP1 and SOP2 genes, which act in cation homeostasis, can be functionally substituted by the Drosophila lethal(2)giant larvae tumor suppressor gene.

By complementation of a salt-sensitive mutant of Saccharomyces cerevisiae, we cloned the SOP1 gene, encoding a 114.5-kDa protein of 1033 amino acids. Cells deleted for SOP1 exhibited sensitivity to sodium stress, but showed no sensitivity to general osmotic stress. Following exposure of sop1Delta cells to NaCl stress, the intracellular Na+ level and the Na+/K+ ratio rose to values significantly higher than in wild type cells. Deletion of SOP2, encoding a protein sharing 54% amino acid identity with Sop1p, produced only slight Na+ sensitivity. Cells carrying a sop1Deltasop2Delta double deletion became, however, hypersensitive to Na+ and exhibited increased sensitivity also to Li+ and K+, suggesting involvement of both SOP1 and SOP2 in cation homeostasis. The predicted amino acid sequences of Sop1p and Sop2p show significant homologies with the cytoskeletal-associated protein encoded by the Drosophila lethal(2)giant larvae tumor suppressor gene. Immunolocalization of Sop1p revealed a cytoplasmic distribution and cell fractionation studies showed that a significant fraction of Sop1p was recovered in a sedimentable fraction of the cytosolic material. Expression of a Drosophila l(2)gl cDNA in the sop1Deltasop2Delta strain partially restored the Na+ tolerance of the cells, indicating a functional relationship between the Sop proteins and the tumor suppressor protein, and a novel function in cell homeostasis for this family of proteins extending from yeast to human.

Adaptor Proteins, Signal Transducing↗

The importance of the glycerol 3-phosphate shuttle during aerobic growth of Saccharomyces cerevisiae.

Maintenance of a cytoplasmic redox balance is a necessity for sustained cellular metabolism. Glycerol formation is the only way by which Saccharomyces cerevisiae can maintain this balance under anaerobic conditions. Aerobically, on the other hand, several different redox adjustment mechanisms exist, one of these being the glycerol 3-phosphate (G3P) shuttle. We have studied the importance of this shuttle under aerobic conditions by comparing growth properties and glycerol formation of a wild-type strain with that of gut2 delta mutants, lacking the FAD-dependent glycerol 3-phosphate dehydrogenase, assuming that the consequent blocking of G3P oxidation is forcing the cells to produce glycerol from G3P. To impose different demands on the redox adjustment capability we used various carbon sources having different degrees of reduction. The results showed that the shuttle was used extensively with reduced substrate such as ethanol, whereas the more oxidized substrates lactate and pyruvate, did not provoke any activity of the shuttle. However, the absence of a functional G3P shuttle did not affect the growth rate or growth yield of the cells, not even during growth on ethanol. Presumably, there must be alternative systems for maintaining a cytoplasmic redox balance, e.g. the so-called external NADH dehydrogenase, located on the outer side of the inner mitochondrial membrane. By comparing the performance of the external NADH dehydrogenase and the G3P shuttle in isolated mitochondria, it was found that the former resulted in high respiratory rates but a comparably low P/O ratio of 1.2, whereas the shuttle gave low rates but a high P/O ratio of 1.7. Our results also demonstrated that of the two isoforms of NAD-dependent glycerol 3-phosphate dehydrogenase, only the enzyme encoded by GPD1 appeared important for the shuttle, since the enhanced glycerol production that occurs in a gut2 delta strain proved dependent on GPD1 but not on GPD2.

Aerobiosis↗

Elevated cytotoxicity in combat veterans with long-term post-traumatic stress disorder: preliminary observations.

Resting immune [WBC and differential cell counts lymphocyte phenotyping (CD2, CD4, CD8, CD16, CD20, and CD56), and NK activity] and endocrine (cortisol, prolactin, growth hormone, and DHEA-SO4) parameters were measured in 10 male, Vietnam combat veterans diagnosed with long-term post-traumatic stress disorder (PTSD) and 9 control Vietnam combat veterans without a PTSD diagnosis but with a comparable history of alcohol abuse. Subjects completed a battery of psychological questionnaires. We report on preliminary observations of the relationship between PTSD and physiological and psychological parameters. With some important exceptions, PTSD patients did not differ from the age-matched control group with regard to hormone levels or lymphocyte phenotypes. However, NK activity was higher in the PTSD population than in the controls. Beck, Mississippi, and Combat Exposure scores were significantly elevated in the PTSD population. In contrast to previous observations in depressed populations, depression (indicated by elevated Beck scores), comorbid with PTSD, was associated with increased natural cytotoxicity.

Adult↗

Ultrasonic determination of the elastic modulus of human cortical bone.

The elastic modulus (Cii) of the cortical bones of 19 individuals (14 femurs and 16 tibias, fixed in formalin) was determined ultrasonically. Elastic moduli were measured at four anatomical positions (anterior, posterior, medial and lateral) and in all three planes of orientation (transverse, longitudinal and radial). The mean tibial Cii (34.11 GPa) was greater than that obtained for femurs (32.52 GPa). The tibial longitudinal plane Cii (34.1 GPa) was significantly greater than the femoral longitudinal plane Cii (32.5 GPa). Cii was significantly higher in the tibia than the femur in both the medial and posterior anatomical positions. The anterior tibia had a significantly lower C11 compared to other positions. Cii was significantly higher in the longitudinal plane than the transverse or radial planes in both the femur and the tibia. There was no consistent difference in modulus between left and right sides. No age effects were observed. There were no significant differences between males and females, or between African Americans and European Americans.

Age Factors↗

The two isoenzymes for yeast NAD+-dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox regulation.

The two homologous genes GPD1 and GPD2 encode the isoenzymes of NAD-dependent glycerol 3-phosphate dehydrogenase in the yeast Saccharomyces cerevisiae. Previous studies showed that GPD1 plays a role in osmoadaptation since its expression is induced by osmotic stress and gpd1 delta mutants are osmosensitive. Here we report that GPD2 has an entirely different physiological role. Expression of GPD2 is not affected by changes in external osmolarity, but is stimulated by anoxic conditions. Mutants lacking GPD2 show poor growth under anaerobic conditions. Mutants deleted for both GPD1 and GPD2 do not produce detectable glycerol, are highly osmosensitive and fail to grow under anoxic conditions. This growth inhibition, which is accompanied by a strong intracellular accumulation of NADH, is relieved by external addition of acetaldehyde, an effective oxidizer of NADH. Thus, glycerol formation is strictly required as a redox sink for excess cytosolic NADH during anaerobic metabolism. The anaerobic induction of GPD2 is independent of the HOG pathway which controls the osmotic induction of GPD1. Expression of GPD2 is also unaffected by ROX1 and ROX3, encoding putative regulators of hypoxic and stress-controlled gene expression. In addition, GPD2 is induced under aerobic conditions by the addition of bisulfite which causes NADH accumulation by inhibiting the final, reductive step in ethanol fermentation and this induction is reversed by addition of acetaldehyde. We conclude that expression of GPD2 is controlled by a novel, oxygen-independent, signalling pathway which is required to regulate metabolism under anoxic conditions.

Adaptation, Physiological↗